Template Letters | Case for Combination Therapy in Pulmonary
Hypertension
This letter is only an example. Please edit the letter to suit your needs and replace [bold]
sections with the appropriate information. It is intended to be sent by a medical professional on
behalf of the patient. The patient should keep an original signed copy for their records.
[PRINT ON MEDICAL CENTER OR INSTITUTION LETTERHEAD]
[TODAY’S DATE]
Re: [PATIENT NAME, DOB]
To Whom It May Concern:
WHO Group 1 pulmonary hypertension, or pulmonary arterial hypertension (PAH), is a highly
fatal disease for which newer therapies have markedly improved quality of life, and have
extended survival from 2.8 years without treatment to an estimated seven to nine years.
As with systemic hypertension, no single therapy is curative. In systemic hypertension, the
combination of drugs has effectively reduced the incidence of stroke, heart attack and renal
disease and it seems clear that an analogous benefit exists in PAH. Despite the greater severity
and immediacy of PAH compared to systemic hypertension, the PAH field is younger and
studies with combination oral drugs are still underway.
In pulmonary hypertension, the use of multiple drugs began with the addition of epoprostenol to
calcium channel blockers in the 1990’s, and now includes combinations of prostacyclins with
phosphodiesterase type-5 (PDE5) inhibitors and with endothelin receptor antagonists (ERAs).
Physicians who care for failing patients with PAH need to be able to try combination therapies
for compassionate use. In our opinion, this should be considered an indication.
Though combination therapy in PAH has been driven by expert consensus and experience, data
is beginning to be generated on the safety and efficacy of this therapeutic strategy. In 2015,
results from the A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in
Pulmonary Arterial Hypertension (AMBITION) clinical trial were published in the New
England Journal of Medicine. This study of 500 participants reported on the safety and efficacy
of initial, upfront combination therapy of an ERA, ambrisentan (Letairis®), and a PDE5,
tadalafil (Adcirca®) compared to each of the therapies used individually (“monotherapy”) on a
time to first event of clinical failure which included:
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All-cause mortality
Hospitalization for worsening pulmonary arterial hypertension
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Disease progression
Unsatisfactory long-term clinical response
Galiè and colleagues reported a 50% reduced risk of this clinical failure composite
endpoint in the combination therapy treatment arm compared to the pooled monotherapy
arms (HR 0.5, 95%CI 0.35-0.72; p<0.001). Statistical significant was maintained when
comparing combination therapy to the ambrisentan (HR 0.48, 95% CI 0.31-0.72, p<0.001) and
tadalafil (HR 0.53, 95% CI 0.34-0.83, p=0.005) treatment arms individually.
The Scientific Leadership Council of the Pulmonary Hypertension Association strongly favors
allowing clinicians to utilize combination therapy in PAH both as an upfront treatment and when
patients fail to adequately improve on monotherapy.
As with cancer which can also be fatal, it seems likely that PAH will ultimately require the use
of two or more therapies in many circumstances in order to prolong life and improve quality. It is
completely reasonable to hold treating physicians to a standard that requires quantification of
failure, which may include 6-minute walk, Doppler echocardiography and right heart
catheterization in some combination, depending on circumstances, in order to reach the threshold
for a waiver to use combination therapy.
Thank you for your time and willingness to review this issue.
Sincerely,
[SIGNATURE]
[PHYSICAN NAME], [DATE]
[ADDRESS]
[PHONE NUMBER]
[FAX NUMBER]
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